Recent studies suggest that nitric oxide(NO) may be important in the pathogenesis of brain injury following cerebral ischemia. Inhibition of NO synthase with arginine analogue N-Nitro-L-arginine metyl ester(L-NAME) reduces infarct size in some rodent models. Therefore, the effects of L-NAME on brain metabolic recovery have been studied in a piglet model of deep hypothermic circulatory arrest (DHCA). Thirty 2-week old piglets underwent core cooling to 15oC nasopharyngeal temperature and 1 hour of deep hypothermic circulatory arrest at 15oC, 45 minutes of rewarming and 3 hours of normothermic reperfusion. Group L-NAME 10mg/kg(n=10) received 10 mg/kg of L-NAME intravenously before cardiopulmonary bypass. Group L-NAME 2mg/kg(n=10) received 2mf/kg of L-NAME in the same way. Group Control(n=10) received no intervention. Recovery of cerebral high energy phosphates and pHi was assessed by magnetic resonance spectroscopy in half the animals in each group. Cerebral blood flow(CBF) and cerebral vascular resistance(CVR) by microspheres, cerebral metabolic rate of oxygen(CMRO2), and the redox state of cytochrome a,a3, oxygenated hemoglobin (HbO2) and deoxygenated hemoglobin(Hb) by near infrared spectroscopy were assessed in the rest. Brain water content was measured in all animals. Use of L-NAME in a piglet model of hypothermic circulatory arrest reduces recovery of cerebral ATP, pHi and cytochrome a,a3 oxidation and increases mean blood pressure, CVR and brain water content. The mechanism for these latter findings is not related to effects on cerebral blood flow. If L-NAME is acting as an inhibitor of NO synthase, NO may be important in metabolic recovery of the brain after DHCA.